First trial of varenicline for vape cessation in the U.S. successful

The first U.S. clinical trial of varenicline for cessation of e-cigarette use shows promising results and calls for larger trials, researchers say.

Researchers from the Yale Cancer Center and the Hollings Cancer Center at the Medical University of South Carolina published the results of their clinical trial of varenicline to help adults quit using e-cigarettes in the American Journal of Preventive Medicine.

The results showed a significant difference between the placebo group and the group receiving the drug. “We saw a 15% difference in quit rates, with the drug group having a 45% quit rate,” said Lisa Fucito, Ph.D., lead author and director of the tobacco treatment service at Yale Cancer Center and Smilow Hospital.

Benjamin Toll, Ph.D., director of the tobacco treatment program at MUSC Health and senior author of the study, said the researchers designed the trial to be as close to real-world conditions as possible — from the people participating in the trial to the type of support they are likely to receive from their primary care physicians.

The publication of their results follows the publication of a trial of cytisinicline for cessation of e-cigarette use. Both drugs work in a similar way. However, varenicline is already available in the US as a generic drug, while cytisinicline has not yet received FDA approval and is currently unavailable to patients.

Varenicline, perhaps better known by its brand name Chantix, is FDA-approved to help adults quit smoking regular cigarettes. But despite the growing number of people using e-cigarettes, there are no approved medication options to help them stop using e-cigarettes.

"People can get very high levels of nicotine exposure with these e-cigarette products and can use them almost constantly throughout the day. So the question we're all asking is, can any pharmacotherapy do this?" Fucito said.

It's a logistical issue. People who smoke cigarettes have to take a cigarette out of the pack and light it. It's easy to track usage. There are also natural stopping points - when a cigarette runs out, it needs to be put out, and when the pack runs out, it needs to be thrown away and a new one bought before smoking again.

E-cigarettes, however, can last more than 5,000 puffs, making it difficult to track consumption but easier to use. Toll said he has patients who describe keeping their e-cigarettes under their pillow so they can vape right before bed and immediately after waking up.

Previous studies have shown that most people who use e-cigarettes want to quit. But it was unclear whether the products used to quit smoking regular cigarettes would work for e-cigarettes.

"We need more pharmacotherapeutic treatments to help manage the very strong physical dependence that can develop from e-cigarette use. People experience significant withdrawal when they try to quit, and that withdrawal is so unpleasant and difficult to manage with behavioral support alone," Fucito said.

A recent Italian study combined pharmacotherapy with intensive weekly behavioral counseling sessions, and the cytisinicline trial also included weekly 10-minute sessions with trained counselors.

In this study, however, the researchers wanted to see how well pharmacotherapy might work in a typical healthcare setting – meaning a patient would likely receive a brief discussion with a GP along with a prescription and information about resources for stopping, but no follow-up consultations.

To recreate this, they developed a self-help smoking cessation guide for patients with practical tools and tips for quitting. A licensed health care professional also met with each patient to explain how to use the drug, offer brief advice, and instruct them to set a quit date one to two weeks after starting the drug.

"We used a lighter approach to reflect the kind of behavioral support you'd likely get if you went to your doctor and asked for help quitting e-cigarettes," Fucito said.

The study also included patients with a history of depression. That was important because Chantix once had a “black box” warning after reports linked the drug to psychiatric side effects. That warning was lifted in 2016 after a very large study found the drug was safe, but Toll and Fucito said the stigma of the warning remains in the minds of both health care professionals and the general public.

"There is still some hesitancy to prescribe this very safe - now generic - drug, and there shouldn't be," Toll said.

None of the participants in this study experienced serious side effects, although a larger study would be needed to confirm this finding. Most side effects were nausea, insomnia, or vivid dreams.

Another piece of good news is that those who stopped using e-cigarettes did not return to smoking regular cigarettes.

"If you have a history of smoking, one of the concerns in this area is that you'll go back to smoking when you stop using e-cigarettes," Toll said. "And we didn't find that."

On the other hand, one potential concern the researchers identified in the results was that people with no history of smoking — in other words, those who have only ever used e-cigarettes — may have a harder time quitting. This may be because this group is more likely to use e-cigarettes consistently throughout the day, thus getting more nicotine into their system.

Larger studies are needed to explore these questions. But this trial should at least give health care providers confidence in prescribing varenicline to patients trying to quit e-cigarette use.

“We want people to come back to this drug,” Fucito explained. “There are people who need help now and who will probably struggle to stop using e-cigarettes on their own because the technology allows for nicotine at levels we’ve never seen before.”